The management and treatment of an infection-prone wound, a surgical site, a surgical incision, or otherwise infection-prone tissues in the body, has three primary objectives: (1) prevention of infection, (2) preservation and/or restoration of function, and (3) preservation and/or restoration of cosmetic appearance. The most important of these objectives is the prevention of infection. Success in the prevention of infection directly affects the healing process and the degree to which function and cosmetic appearance can be preserved and/or restored.
The number and virulence of bacteria present at a site are critical determinants of whether the site becomes infected. Experimental evidence suggests that a critical level of bacteria is approximately 105 organisms per gram of tissue. Below this level, a site or a tissue typically heals; at levels greater than 105 bacteria per gram of tissue, infections often develop. Dirty wounds, or wounds that have not been treated within six hours, are likely to be contaminated with bacteria at levels that are higher than the critical level. Reducing the number of bacteria in and around the wound is critical for avoiding infection and expediting wound healing.
Many of the viruses, bacteria, parasites, and fungi that can invade the human body and its tissues are also capable of attacking the surface or interior of the eye. The eye is a complex organ of many parts. Infectious eye diseases can be categorized in two ways. First, physicians normally address the part of the eye that is infected or inflamed. Conjunctivitis, for example, is an inflammation of the conjunctiva, the membrane of the inner eyelid and the inner corner of the eye's surface. Other possible locations of infection and inflammation include the eyelid (blepharitis), the eyelash (stye), the cornea (keratitis), the oil gland of the eyelid (chalazion), the lacrimal sac at the inner corner of the eye (dacryocystitis), the liquid inside the eye (vitritis), the retina and the blood vessels that feed it (chorioretinitis), or the optic nerve (neuroretinitis). Second, eye infections are also classified according to what is causing them.
Ocular histoplasmosis syndrome (OHS), for example, is caused by a fungus (the condition is also called chorioretinitis). It generally attacks the blood supply of the retina, on the inner rear surface of the eye. Fungal eye infections are extremely rare, but they can be very serious. The most common way for someone to develop a fungal eye infection is as a result of an eye injury, particularly if the injury was caused by plant material such as a stick or a thorn. All types of fungal eye infections must be treated with prescription antifungal medication, usually for several weeks to months. Natamycin is a topical antifungal medication that works well for fungal infections involving the outer layer of the eye, particularly those caused by fungi such as Aspergillus Candida, and Fusarium. Endophthalmitis is an infection of the inside of the eye (the vitreous and/or aqueous humor). There are two types of endophthalmitis: exogenous and endogenous. Exogenous fungal endophthalmitis occurs after fungal spores enter the eye from an external source. Endogenous endophthalmitis occurs when a bloodstream infection (for example, candidemia) spreads to one or both eyes.
Parasites such as Acanthamoeba which are a microscopic, free-living ameba (single-celled living organism) commonly found in the environment can cause rare, but severe, illness. Acanthamoeba causes three main types of illness involving the eye (Acanthamoeba keratitis), the brain and spinal cord (Granulomatous Encephalitis), and infections that can spread throughout the entire body (disseminated infection). Acanthamoeba is found worldwide. Most commonly, Acanthamoeba is found in soil, dust, fresh water sources (such as lakes, rivers, and hot springs), in brackish water (such as a marsh), and sea water. Acanthamoeba can also be found in swimming pools, hot tubs, drinking water systems (for example, slime layers in pipes and taps), as well as in heating, ventilating, and air conditioning (HVAC) systems and humidifiers. Acanthamoeba keratitis infection has been linked to contact lens use, although people who do not use contact lenses can also become infected. Poor contact lens hygiene or wearing contact lenses during swimming, hot tub use, or showering may increase the risk of Acanthamoeba entering the eye and causing a serious infection. However, contact lens wearers who practice proper lens care can also develop infection.
The most common eye infection is conjunctivitis caused by an adenovirus, picornavirus, e.g., enterovirus 70 and coxsackievirus A24, rubella virus, rubeola virus, herpes virues, varicella-zoster virus, Epstein-Barr virus, and bacteria such as gonorrhea or chlamydia. This type of infectious conjunctivitis is sometimes called pinkeye and is most common in children. Viral conjunctivitis is contagious because the virus can be spread from the eye to hands that then touch doorknobs and other surfaces that other people use. Hands can become contaminated by coming in contact with infectious tears, eye discharge, fecal matter, or respiratory discharges. There are other causes of infectious conjunctivitis, such as bacteria like Staphylococcus aureus. Bacterial infections occur most commonly in children and tend to result in longer-lasting cases of pinkeye. The most common types of bacteria that cause bacterial conjunctivitis include Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Pseudomonas aeruginosa. Bacterial conjunctivitis is highly contagious and is spread through direct hand-to-eye contact from contaminated hands and usually produces a thick eye discharge or pus and can affect one or both eyes. Globally, the bacterium Chlamydia trachomatis is the leading cause of preventable blindness of infectious origin. Trachoma is a chronic follicular conjunctivitis, which is transmitted from person-to-person, through shared items or by flies.
Methicillin-resistant Staphylococcus aureus (MRSA) infection is caused by Staphylococcus aureus bacteria—often called “staph.” Decades ago, strains of staph emerged in hospitals that were resistant to the broad-spectrum antibiotics commonly used to treat them. These antibiotics include methicillin and other more common antibiotics such as oxacillin, penicillin, and amoxicillin. Dubbed MRSA, it was one of the first germs to be resistant to all but the most powerful drugs.
Staph bacteria are generally harmless unless they enter the body through a cut or other wound. In older adults and people who are ill or have weakened immune systems, ordinary staph infections can cause serious illness. Staph infections, including MRSA, occur most frequently among persons in hospitals and healthcare facilities, such as nursing homes and dialysis centers, who have weakened immune systems; however, in the 1990s, a type of MRSA began appearing in the wider community. Today, that form of staph, known as community-associated MRSA, or CA-MRSA, and is responsible for many serious skin and soft tissue infections and for a serious form of pneumonia. If not treated properly, MRSA infection can be fatal.
Eye infections caused by MRSA are on the rise. MRSA infections are spreading rapidly in the United States and worldwide. According to the Center for Disease Control and Prevention (CDC), the proportion of infections that are antimicrobial resistant has been growing. In 1974, MRSA infections accounted for two percent of the total number of staph infections; in 1995 it was 22%; and in 2004 it was nearly 63%. Additionally, recent research has suggested that 30-50% of the population carries MRSA colonies on their bodies all the time, helping to facilitate the spread of infection.
Vancomycin is one of the few antibiotics still effective against hospital strains of MRSA infection, although the drug is no longer effective in every case. Several drugs continue to work against MRSA, but MRSA is a rapidly evolving bacterium, and it may be a matter of time before it, too, becomes resistant to most antibiotics. New treatments for infection are needed.
Chlorhexidine is a chemical antiseptic, and it combats both gram positive and gram negative microbes. It is bacteriostatic, hampering the growth of bacteria, and bacteriocidal, killing bacteria. It is often used as an active ingredient in mouthwash designed to kill dental plaque and other oral bacteria. Chlorhexidine also has non-dental applications. For example, it is used for general skin cleansing, as a surgical scrub, and as a pre-operative skin preparation. Chlorhexidine is typically used in the form of acetate, gluconate, or hydrochloride, either alone or in combination with other antiseptics such as cetrimide. The use of chlorhexidine has been found to be surprisingly non-toxic in topical treatment of the eye. This lack of toxicity facilitates the use of chlorhexidine in contexts that were not previously thought possible. The present invention is based on new unexpected findings that demonstrate the ability of the provided compound to significantly reduce ophthalmic inflammation and infection.
See, for example, U.S. Published Application No. 2011-0288507A and U.S. Published Application No. 2011-0097372A, both of which are incorporated herein, by reference, in their entireties.